Unravelling the genetic architecture of inflammatory bowel disease multiplex families with rare and common variant polygenic risk scores.

Background And Aims: Inflammatory bowel disease (IBD) often affects multiple relatives, pointing towards shared genetic and/or environmental factors. This study evaluates the importance of known IBD risk variants, and of genetic determinants of smoking in such multiplex families.

Methods: We studied 65 IBD multiplex families, comprising 146 Crohn's disease [CD], 33 ulcerative colitis [UC], and 111 unaffected relatives.

Optimizing the switch from escalated intravenous to subcutaneous infliximab: a population pharmacokinetics-pharmacodynamics study.

Background And Aims: It remains unclear if patients on escalated intravenous (IV) infliximab can switch to standard subcutaneous (SC) infliximab CT-P13 of 120 mg bi-weekly (Q2W) injections without losing therapeutic response. This study investigates the dose-exposure-response relationship during the IV-to-SC switching of infliximab in Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Data were collected from healthy volunteers and patients with CD and UC in different Phase I studies.

Effect of five dietary emulsifiers on inflammation, permeability, and the gut microbiome: a placebo-controlled randomized trial.

Background And Aims: Dietary emulsifier consumption might promote intestinal inflammation, eventually leading to inflammatory bowel diseases. However human data are scarce and involve a limited number of emulsifiers. We studied the effects of an emulsifier-free diet (EFD) and specific emulsifier supplementation.

Bowel Urgency in Crohn's Disease: Effects of Mirikizumab in a Randomized Controlled Phase 3 Study.

Background And Aims: Bowel urgency (BU) is an underrecognized and debilitating symptom of Crohn's disease. Mirikizumab, an interleukin-23p19 inhibitor, is efficacious for BU resolution in ulcerative colitis. We evaluated the efficacy of mirikizumab in achieving early BU response and remission among participants with Crohn's disease enrolled in the phase 3 VIVID-1 study.

Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Biologic-Naïve Patients With Early or Late Crohn's Disease: Results From the EVOLVE Expansion Study.

Background: We evaluated the real-world effectiveness and safety of vedolizumab and ustekinumab as first-line biologics in patients with Crohn's disease (CD), by disease duration.

Methods: EVOLVE Expansion (ClinicalTrials.gov, NCT05056441) was a retrospective medical chart review study in Australia, Belgium, and Switzerland.

Assessment of PredictSURE IBD Assay in a Multinational Cohort of Patients With Inflammatory Bowel Disease.

Background And Aims: PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination.

Methods: One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling.

Ulcerative colitis disease severity affects the speed of symptom relief under filgotinib treatment: a post hoc analysis of the phase 2b/3 SELECTION study.

Background/aims: Filgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). This study aimed to assess symptomatic response with filgotinib 200 mg (FIL200) according to disease severity using baseline partial Mayo Clinic Score (pMCS).

Methods: In the phase 2b/3 SELECTION study (NCT02914522), adults with moderate-to-severe UC were randomized to receive FIL200, filgotinib 100 mg, or placebo for 11 weeks in induction studies A (biologic-naive) and B (biologic-experienced).

Gaps between European Crohn's and Colitis Organisation quality standards of care and the real world on diagnosis and monitoring inflammatory bowel disease across Europe: results from the E-QUALITY survey.

Background And Aims: Quality of care in inflammatory bowel disease (IBD) management is crucial for early detection and prevention of disease progression and complications. The European Crohn's and Colitis Organisation (ECCO) developed evidence-based recommendations and quality of care (QoC) standards for IBD management, but gaps between these standards and real-world practices still exist. The E-QUALITY task force aimed to evaluate processes related to quality standards of IBD diagnosis and management across European institutions and identify barriers to meet ECCO QoC standards.

ECCO Topical Review on Pouch Disorders.

Background: Pouch disorders are common and may present with symptoms of increased stool frequency, urgency, incontinence, pelvic cramping, obstructed defecation, and perianal drainage, which can result in poor sleep, fatigue, and disability. This topical review aims to offer expert consensus practice recommendations for the diagnosis and management of the most common inflammatory, functional, structural, and neoplastic J-pouch disorders.

Methods: A multidisciplinary panel of gastroenterologists and colorectal surgeons performed a systematic review of the relevant literature on pouch disorders and developed current practice positions.

Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Biologic-Naive Patients With Crohn's Disease By Disease Location: Results from the EVOLVE Expansion Study.

Goals: This analysis compared the real-world effectiveness and safety of vedolizumab versus ustekinumab in biologic-naive patients by CD location.

Background: Crohn's disease (CD) location may affect disease course and treatment decisions.

Study: Medical charts of biologic-naive patients with CD aged 18 years or older initiating vedolizumab or ustekinumab were analyzed in the multicenter, observational, retrospective EVOLVE Expansion study.

HER2, HER3, and Mismatch Repair Protein Expression in Stage IV Small Bowel Adenocarcinoma: Results From a Multicenter Series.

Small bowel adenocarcinoma (SBA) is a rare and aggressive malignancy. One-third of SBA cases are diagnosed at an advanced stage, often with limited treatment options. Recent clinical trials have underscored the importance of testing predictive biomarkers for therapy response in advanced solid tumors, particularly with respect to antibody-drug conjugates and immunotherapy.

Gaps between European Crohn's Colitis Organisation quality standards of care and the real world on structure of IBD units across Europe: results from E-QUALITY survey.

Background And Aims: Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, require an interdisciplinary approach for diagnosis, monitoring, and management. The European Crohn's and Colitis Organisation (ECCO) has developed evidence-based recommendations and quality care standards for IBD management, but gaps between these standards and real-world practice persist. The E-QUALITY task force aimed to evaluate the structure, processes, and outcomes of IBD units across Europe and identify barriers to achieving ECCO quality standards.

The Development of a Multidisciplinary Care Pathway for Patients with Inflammatory Bowel Disease Before, During and After Pregnancy.

: Recent advancements have significantly enhanced our understanding of the interplay between inflammatory bowel disease (IBD) and reproductive health. While international organizations provide guidelines for best practices, translating them into actionable strategies is crucial. This study aimed to develop a comprehensive care pathway to enhance preconception counselling and support for patients with IBD in the perinatal period, ensuring they receive optimal expert care.

Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects.

Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis.

Drug tissue concentration and STAT3 modulation as determinants of tofacitinib response in ulcerative colitis.

Introduction: Inflammatory bowel disease management has advanced with therapies like Janus kinase inhibitors (JAKi). Despite their promise, JAKi pharmacokinetic-pharmacodynamic (PK-PD) profiles and tissue-level effects remain underexplored. This study investigates tissue and serum tofacitinib levels, their correlation with therapeutic efficacy, and molecular mechanisms underlying treatment response.

Effect of Risankizumab Induction and Maintenance Therapy on the Rate of Hospitalization in Patients with Crohn's Disease.

Background And Aims: In phase 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) trials, risankizumab was shown to benefit symptom and endoscopic defined outcomes in patients with Crohn's disease (CD). We examined the effects of risankizumab on the incidence of CD-related hospitalizations in these studies.

Methods: Patients with active CD were randomized to intravenous (IV) risankizumab 600 or 1200 mg, or placebo at weeks 0, 4, and 8 in the 12-week induction studies.

Serum extracellular RNAs as a noninvasive approach to differentiate inflammatory bowel disease subtypes: a proof-of-concept study.

Background And Aims: Extracellular RNAs (exRNAs), including in serum, show potential as noninvasive biomarkers. However, their (patho)physiological role is still not fully understood. In this study, we characterized serum exRNAs in patients with inflammatory bowel diseases (IBDs) and evaluated their ability to differentiate ulcerative colitis (UC) from Crohn's disease (CD).

No Increased Risk of Venous Thromboembolism or Infectious Complications after Janus Kinase Inhibitor Exposure in Patients with Ulcerative Colitis Undergoing Surgery.

Introduction: Total colectomy for ulcerative colitis (UC) is associated with postoperative morbidity, including venous thromboembolic events (VTE). In light of recent concerns about increased major adverse events associated with Janus kinase (JAK) inhibitor exposure, we aimed to evaluate the postoperative VTE risk as well as other complications in UC patients undergoing colectomy.

Methods: This single-center retrospective cohort study included all UC patients who underwent (procto)colectomy between 2013 and March 2022 and documented the 180-day postoperative non-infectious and infectious complications.

Extended Risankizumab Treatment in Patients With Crohn's Disease Who Did Not Achieve Clinical Response to Induction Treatment.

Background & Aims: The efficacy and safety of extended treatment with risankizumab (RZB), an anti-interleukin-23 p19 monoclonal antibody, were evaluated in patients with moderate to severe Crohn's disease (CD) who did not achieve clinical response to 12 weeks (W) RZB induction treatment ('initial nonresponders').

Methods: Initial nonresponders to intravenous (IV) RZB induction (600 mg or 1200 mg at W0, W4, and W8) were rerandomized 1:1:1 to receive extended blinded RZB treatment (1200 mg IV at W12, W16, and W20, or subcutaneous [SC] 180 mg or 360 mg at W12 and W20). Patients with clinical response to SC RZB at W24 ('delayed responders') continued their dose in FORTIFY.

Ileal pouch-anal anastomosis for ulcerative colitis: 30-year analysis on surgical evolution and patient outcome.

Background: Proctocolectomy with ileal pouch-anal anastomosis is the treatment of choice for patients with ulcerative colitis with medical refractory disease or dysplasia. The aim of this research was to describe the evolution of ileal pouch-anal anastomosis surgery and surgical outcomes over a three-decade interval in a high-volume referral centre.

Methods: All consecutive patients undergoing ileal pouch-anal anastomosis for ulcerative colitis between 1990 and 2022 at the University Hospitals of Leuven were retrospectively included.

Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.

Background And Aims: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).

Methods: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo.

Early Endoscopic Outcomes After Risankizumab Are Associated With Fewer Hospitalizations and Surgeries in Crohn's Disease.

Background And Aims: We evaluated the association between endoscopic outcomes following risankizumab induction and subsequent rates of hospitalization and surgery through 52 weeks of risankizumab (both doses) maintenance therapy in patients with Crohn's disease (CD).

Methods: Patients with moderately to severely active CD and clinical response to 12-week risankizumab induction were rerandomized to continued therapy or drug withdrawal in the phase 3 FORTIFY maintenance trial. Incidence rates (events/100 person-years) of CD-related hospitalization and surgery, and the composite of both, through 52 weeks of maintenance were compared between patients achieving vs not achieving predefined endoscopic outcomes following induction.

Radiation exposure in patients with inflammatory bowel disease.

Background And Aims: Radiological imaging is crucial for diagnosing and monitoring patients with inflammatory bowel diseases (IBD). With increasing awareness of radiation risks, imaging doses should be "as low as reasonably achievable," with a risk level that one should try to stay underneath 75 mSv. However, real-world data on cumulative exposure are limited.

Dietary Carrageenan Amplifies the Inflammatory Profile, but not Permeability, of Intestinal Epithelial Cells from Patients With Crohn's Disease.

Background: The consumption of ultra-processed foods has increased significantly worldwide and is associated with the rise in inflammatory bowel diseases. However, any causative factors and their underlying mechanisms are yet to be identified. This study aimed to further elucidate whether different types of the dietary emulsifier carrageenan (CGN) can alter the permeability and inflammatory state of the intestinal epithelium.